Building a molecular computer for the body

The biocomputer may be used in the future to screen DNA libraries and accelerate understanding of how DNA works.A group of scientists headed by Prof. Ehud Shapiro at the Weizmann Institute of Science has used biological molecules to create a …

The biocomputer may be used in the future to screen DNA libraries and accelerate understanding of how DNA works.A group of scientists headed by Prof. Ehud Shapiro at the Weizmann Institute of Science has used biological molecules to create a tiny computer in a test tube.

This biological computer is so small that a trillion such computers coexist and compute in parallel, in a drop the size of one-tenth of a milliliter of solution at room temperature. Collectively, the computers perform a billion operations per second with greater than 99.8 percent accuracy while requiring less than a billionth of a watt of power.

The nanocomputer is too simple to have immediate applications; however, it may make possible future computers that can operate within the human body in various ways. The inventors believe it could ultimately lead to a device capable of processing DNA inside the body, finding abnormalities and creating healing drugs. The model could also form the basis of computers that could be used to screen DNA libraries in parallel without sequencing each molecule, which could speed up the acquisition of knowledge about DNA.

DNA sequencing is part of the task of cracking the genetic code of organisms as diverse as the pneumonia bug, the tomato and the human body to discover more about the way they function.

For “hardware,” the computer uses two naturally occurring enzymes that manipulate DNA. When mixed together in a solution, the software and hardware molecules operate together on the input molecule to create the output molecule, forming a simple mathematical computing machine, known as a finite automaton. The biocomputer can be programmed to perform several simple tasks by choosing different software molecules to be mixed in solution. For instance, it can detect whether, in a molecule encoded with a list made of zeros and ones, all the zeros come before all the ones.

“The living cell contains incredible molecular machines that manipulate information-encoding molecules such as DNA and RNA in ways that are fundamentally very similar to (the way a computer works),” said Prof. Shapiro of the Institute’s computer science and applied mathematics department and the biological chemistry department. “Since we don’t know how to effectively modify these machines or create new ones just yet, the trick is to find naturally existing machines that, when combined, can be steered to actually compute.”

Although other researchers have experimented with DNA computing techniques, Shapiro and his colleagues claim that their system is the first programmable autonomous computing machine in which the input, output, software and hardware are all made of biological molecules.

DNA can hold more information in a cubic centimeter than a trillion CDs. The double helix molecule that contains human genes stores data on four chemical bases – known by the letters A, T, C and G – giving it massive memory capability that scientists are only just beginning to tap into.

As the lab work progressed, Shapiro and his team realized that the computer they built could be programmed to perform different tasks. The software molecules, together with two “output display” molecules used to show the final result of the computation, can be used to create a total of 765 software programs, including the “zeros before ones” test.

The computer created by Shapiro’s team uses the four DNA bases to encode the input data as well as the program underlying the computer “software.” Both input and software molecules are designed to have one DNA strand longer than the other, resulting in a single-strand overhang called a “sticky end.” Two molecules with complementary sticky ends can temporarily stick to each other, allowing the binding enzyme to permanently seal them into one molecule.

The sticky end of the input molecule encodes the current symbol and the current state of the computation, whereas the sticky end of each “software” molecule is designed to detect a particular state-symbol combination. A two-state, two-symbol automaton has four such combinations. For each combination the computer has two possible next moves, to remain in the same state or to change to the other state, allowing eight software molecules to cover all possibilities.

Prof. Shapiro was involved with the Japanese Fifth Generation Computer Project during the ’80s and published numerous scientific papers in the area of concurrent logic programming languages. In the early ’90s, Shapiro’s innovative research in programming languages led to the establishment of Ubique, a company that develops interactive online environments. Shapiro’s design of a universal molecular computer, which inspired the creation of the molecular automaton, was awarded a U.S. patent.